S117: CHEMOTHERAPY-FREE TREATMENT WITH INOTUZUMAB OZOGAMICIN AND BLINATUMOMAB FOR OLDER ADULTS WITH NEWLY-DIAGNOSED, PH-NEGATIVE, CD22-POSITIVE, B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: ALLIANCE A041703
Authors: Matthew Wieduwilt, Jun Yin, Oudom Kour, Rebecca Teske, Wendy Stock, Ken Byrd, Kimberly Doucette, James Mangan, Gregory Masters, Alice Mims, Katarzyna Jamieson, Shira Dinner, Ali Bseiso, Geoffrey Uy, Harry Erba, Mark Litzow, Richard Stone
Journal: HemaSphere (2023)

Background: Older adult patients (pts) with Philadelphia-chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) have poor survival with chemotherapy. The anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (InO) and anti-CD19/CD3 T-cell engager blinatumomab (blina) were each superior to conventional chemotherapy in Phase III studies in relapsed/refractory B-ALL. Because InO induces high CR rates and blina can induce durable remissions in low burden disease, we conducted a Phase II trial of induction InO then blina for older adults with newly-diagnosed (ND), Ph-, B-lineage ALL. Aims: The primary aim was to estimate the 1-year(yr) event-free survival (EFS) in older patients with ND, Ph-, B-lineage ALL treated with sequential InO induction then blina consolidation. Methods: Eligible were pts ≥60 years old with ND, Ph-, CD22+ (≥20% of lymphoblasts) B-lineage ALL without plan for allogeneic HCT (alloHCT) at registration. Pts with CNS leukemia or liver disease were excluded. Induction IA was InO 0.8 mg/m2 day(d) 1, 0.5 mg/m2 d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts reduced by ≥50% or cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m2 d1, d8, d15 IV; 28d cycle) or IC if not in CR/CRi (InO 0.8 mg/m2 d1, d8, d15 IV; 28d cycle). Those without cytoreduction to IA proceeded directly to Course II blina. Pts without events in Induction IA/B/C received Course II blina CIV (9 mcg/d x 7d then 28 mcg/d x 21d; 14d break; 28 mcg/d x28d). Pts with CR/CRi to InO received 2 more 28d cycles of blina, others received 3 more. CNS prophylaxis was methotrexate 15 mg intrathecal x 8 doses. No maintenance was given. The primary endpoint was 1-yr EFS with a lower limit of a 90% CI for 1-yr EFS >10% defined as success. EFS was the time from therapy start to failure to achieve CR/CRh/CRi by end course II, progression on therapy prior to end course II, relapse, or death, whichever occurred first. Results: Thirty-three eligible pts were treated (1 ineligible due to 2nd active malignancy). The median age was 71 years (range 60-84). Median WBC count was 3,200/mcl (range 6-38,000). Median CD22 expression was 92% (range 21-100%). Eight pts had therapy-related ALL. The cumulative CR rates through Induction IA/B/C and Course II were 85% and 97%, respectively (Table). With median follow up of 22 mo, the 1-yr EFS was 75% (95% CI 61-92%). The 2-sided 90% CI was 63-89% for 1-yr EFS with lower bound above 10% indicating regimen success. Twelve pts had events: 9 relapses, 2 deaths in remission (1 during blina, 1 after alloHCT), and 1 death without remission from respiratory failure with reported sinusoidal occlusion syndrome of liver. The 1-yr OS was 84% (95% CI 72-98%). Nine pts have died, 6 after relapse. Common Grade 3+ adverse events occurring in >10% of pts were neutropenia (88%), thrombocytopenia (73%), anemia (42%), leukopenia (39%), lymphopenia (27%), febrile neutropenia (21%), and encephalopathy (12%). Summary/Conclusion: InO induction then blinatumomab consolidation is highly active, tolerable therapy for ND, Ph-, CD22+ B-lineage ALL with durable remissions in the majority of pts. The regimen may be considered for older adults with ND, Ph-, CD22+ B-lineage ALL and a comparator regimen for future studies. Support: U10CA180821, U10CA180882, U10CA180820 https://acknowledgments.alliancefound.org. NCT03739814 - N=33 Induction InO I A/B/C Blinatumomab Course II Composite CR* 28 (85%) 32 (97%) CR 15 (45%) 19 (58%) CRh 11 (33%) 12 (36%) CRi 2 (6%) 1 (3%) Refractory 3 (9%)᛭ - Survival 1-yr EFS 75% (95% CI 61-92%) 1-yr OS 84% (95% CI 72-92%) *CR+CRh+CRi᛭ 1 completed IA only, 2 proceeded to course II Keywords: Acute lymphoblastic leukemia, Targeted therapy, B cell acute lymphoblastic leukemia, ALL